The public health use of optimally fluoridated drinking water which is widely recognized for reducing the prevalence of dental caries in children and adults. Because of these known benefits, fluoride has been added to an increasing number of dental products and restorative materials as a means of further reducing the prevalence of dental caries. The ready availability of fluoridated dental products and their indiscriminant use by the general population has led to speculation that exposure to these increasingly higher doses of fluoride may result in a narrowing of the limits between the therapeutic and toxic levels of fluoride. This narrowing margin is of particular concern in persons who may not have the ability to efficiently metabolize and excrete fluoride from the body. The purpose of this investigation is to assess the safety of the public health use of fluorides using current scientific methodologies. Specific populations will be targeted for this investigation under the assumption that they have a higher likelihood of expressing any adverse effects which have been or could be associated with increasing fluoride exposure. The populations are: 1, adults and children with lifetime exposure to elevated levels of naturally fluoridated water; 2, children and adults afflicted with diabetes mellitus residing in an optimally fluoridated community; 3, children and adults afflicted with chronic renal disease residing in an optimally fluoridated community; and 4, adults who have been exposed to high doses of fluoride as a means of treating osteoporosis. The aims of this investigation will be to determine the pharmacologic, genotoxic and dental effects of fluoride, if any, on these specific populations. Blood and urine samples will be collected and analyzed to determine the possible pharmacologic and genotoxic effects while visual examinations of the dentition will be used to determine if the prevalence of dental fluorosis is increasing.